Paliperidone and Lithium in the Treatment of Suicidality - Treatment Indication and Epigenetic Regulation (AFSP)

This study has been completed.
Sponsor:
Collaborators:
American Foundation for Suicide Prevention
Ortho-McNeil Janssen Scientific Affairs, LLC
Information provided by (Responsible Party):
Dr. Richard Shelton, University of Alabama at Birmingham
ClinicalTrials.gov Identifier:
NCT01134731
First received: May 20, 2010
Last updated: February 3, 2016
Last verified: February 2016
  Purpose

The study aims to use a combined clinical and translational approach to identify an efficient pharmacotherapy for the acute management of suicidality and the epigenetic regulation associated with the treatment.The primary objective is a clinical trial to compare the efficacy of paliperidone versus lithium and placebo as adjunctive therapy to the standard of care antidepressants in the acute management of suicidality in depressed subjects.

Specific Aims 1 and 2 are described in detail below. Analysis for Specific Aim 2 is still underway.


Condition Intervention Phase
Major Depressive Disorder
Suicidal Ideation
Drug: paliperidone
Drug: lithium
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Paliperidone and Lithium in the Treatment of Suicidality - Treatment Indication and Epigenetic Regulation

Resource links provided by NLM:


Further study details as provided by University of Alabama at Birmingham:

Primary Outcome Measures:
  • Mean Score of Beck Scale for Suicidal Ideation of Three Treatment Groups (Paliperidone, Lithium and Placebo) After 3 Months of Treatment [ Time Frame: baseline to 12 weeks ] [ Designated as safety issue: No ]
    The Beck Scale for Suicidal Ideation will be used to measure the efficacy of the study drugs. The primary outcome measure is the Beck Suicide Scale Self Report. The primary outcome measure is the Beck Suicide Scale Self Report. It has 21 questions (subscales) with values ranging from 0-2. Therefore the total score ranges from 0-42, with lower scores indicating better outcomes. The subscales were summed to achieve a total score.


Secondary Outcome Measures:
  • Mean Score of Montgomery-Asberg Depression Scale of Three Treatment Groups (Paliperidone, Lithium and Placebo) After 3 Months of Treatment [ Time Frame: baseline to 12 weeks ] [ Designated as safety issue: No ]
    The Montgomery-Asberg Depression Rating Scale will be used to measure depressive symptoms to determine the efficacy of the study drugs. It has 10 items (subscales) ranging from 0-6. Therefore the total score ranges from 0-60, with lower scores indicating better outcomes. The subscales were summed for a total score.


Enrollment: 54
Study Start Date: May 2010
Study Completion Date: February 2014
Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: paliperidone
dose escalation , levels 1-5 daily dosing ranged from 1-5mg
Drug: paliperidone
1-5 mg daily (QD)
Active Comparator: lithium
dose escalation, level 1-5 daily dosing 300-1500mg
Drug: lithium
300-1500mg QD
Placebo Comparator: placebo
1-5 placebo capsules
Drug: Placebo
1-5 placebo capsules

Detailed Description:

Specific Aim 1: The atypical antipsychotic, paliperidone, when initiated simultaneously with an antidepressant, is superior to lithium plus antidepressant in the early intervention of suicidality in patients with Major Depressive Disorder (MDD). The goal of this aim is to examine the clinical efficacy of paliperidone in reducing suicidality, with a focus on early intervention. The hypothesis is based on our recently completed pilot study in which we found that the atypical antipsychotic, risperidone, had a rapid onset of action to reduce suicidality in patients with MDD. In view of a shortage in acute pharmacological management of suicidality, this study will provide an important new treatment option for the life threatening psychiatric condition.

Specific Aim 2: Both paliperidone and lithium regulate epigenetics by stabilizing DNA methylation, which is correlated with inhibition of glycogen synthase kinase-3 (GSK3) activity and improved clinical symptoms. This exploratory aim is developed based on the recent findings that DNA methylation is involved in regulation of mood, behavior, and cognition, and the enzyme of this epigenetic mechanism - DNA methyltransferase-1 (DNMT1) is regulated by the therapeutic target Glycogen synthase kinase 3 (GSK3). We will measure the expression of DNMTs and DNA methylation of global DNA, Brain-derived neurotrophic factor (BDNF), and Tropomyosin receptor kinase B (TrkB) in peripheral blood before and after study drug treatment, and analyze their correlation with GSK3 activity and clinical symptoms in response to treatment. Outcomes from this study will provide important new information in future development of more effective treatment options for suicidality targeting epigenetic regulation.

  Eligibility

Ages Eligible for Study:   19 Years to 65 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male and female subjects who are able to provide informed consent
  2. 19-65 years of age
  3. Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) diagnosis of MDD by MINI International Neuropsychiatric Interview (MINI) and confirmed by psychiatric interview
  4. Currently experiencing a depressive episode with suicidality (defined as having current suicidal thoughts occurring at least 3 out of 7 days in a week).
  5. Montgomery-Asberg Depression Rating Scale (MADRS) must include a total score > 25 and a suicidal sub-score > 4.

Exclusion Criteria:

  1. Depressed patients without suicidality, patients with severe psychotic features or with primary diagnoses of bipolar disorder (BD), schizophrenia, schizoaffective disorder, or generalized anxiety disorder (GAD), and subjects who have been taking lithium or an antipsychotic in the past 2 weeks
  2. Those with uncontrolled medical illnesses. Participants must be on any new medications for at least 30 days to be considered medically stable.
  3. For patients with panic disorder, post-traumatic stress disorder (PTSD), borderline personality disorder (BPD), etc. be sure that MDD is the primary diagnosis. When in doubt, decisions will be made on a case-by-case basis.
  4. Pregnant women.
  5. Allergic to paliperidone, to any other ingredient in paliperidone ER or paliperidone palmitate, or to risperidone.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01134731

Locations
United States, Alabama
UAB
Birmingham, Alabama, United States, 35294
Sponsors and Collaborators
University of Alabama at Birmingham
American Foundation for Suicide Prevention
Ortho-McNeil Janssen Scientific Affairs, LLC
Investigators
Principal Investigator: Richard C Shelton, M.D. University of Alabama at Birmingham
  More Information

Responsible Party: Dr. Richard Shelton, Professor, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT01134731     History of Changes
Other Study ID Numbers: F100329001 
Study First Received: May 20, 2010
Results First Received: May 26, 2015
Last Updated: February 3, 2016
Health Authority: United States: Institutional Review Board
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by University of Alabama at Birmingham:
depression
suicidality
Major Depressive Disorder, current episode, with suicidality

Additional relevant MeSH terms:
Depressive Disorder
Depression
Depressive Disorder, Major
Suicidal Ideation
Mood Disorders
Mental Disorders
Behavioral Symptoms
Suicide
Self-Injurious Behavior
Lithium Carbonate
Paliperidone Palmitate
Antidepressive Agents
Psychotropic Drugs
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Antipsychotic Agents
Serotonin 5-HT2 Receptor Antagonists
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Dopamine D2 Receptor Antagonists
Dopamine Antagonists
Dopamine Agents

ClinicalTrials.gov processed this record on August 23, 2016